Signals involved in T cell activation. I. Phorbol esters enhance responsiveness but cannot replace intact accessory cells in the induction of mitogen-stimulated T cell proliferation

Journal Article · Fri Nov 01 04:00:00 EST 1985 · J. Immunol.; (United States)

OSTI ID:6935705

Davis, L; Lipsky, P E

The role of accessory cells (AC) in the initiation of mitogen-induced T cell proliferation was examined by comparing the effect of intact macrophages (M phi) with that of 4-..beta..-phorbol 12-myristate 13-acetate (PMA). In high-density cultures, purified guinea pig T cells failed to proliferate in response to stimulation with phytohemagglutinin (PHA), concanavalin A (Con A), or PMA alone. The addition of M phi to PHA or Con A but not PMA-stimulated cultures restored T cell proliferation. The addition of PMA to high-density T cell cultures stimulated with PHA or Con A also permitted (/sup 3/H)thymidine incorporation, but was less effective than intact M phi in this regard. This action of PMA was dependent on the small number of Ac contaminating the T cell cultures as evidenced by the finding that PMA could not support mitogen responsiveness of T cells that had been depleted of Ia-bearing cells by panning, even when these cells were cultured at high density. A low-density culture system was used to examine in greater detail the possibility that PMA could completely substitute for M phi in promoting T cells activation. In low-density cultures, mitogen-induced T cell proliferation required intact M phi. These results support a model of T cell activation in which AC play at least two distinct roles. The initiation of the response requires a signal conveyed by an intact M phi, which cannot be provided by either a M phi supernatant factor or PMA. The response can be amplified by additional M phi or M phi supernatant factors. PMA can substitute for M phi in this regard and can provide the signal necessary for amplification of T cell proliferation supported by small numbers of intact AC.

• Research Organization: Univ. of Texas Health Science Center, Dallas
• OSTI ID: 6935705
• Journal Information: J. Immunol.; (United States), Journal Name: J. Immunol.; (United States) Vol. 135:5; ISSN JOIMA
• Country of Publication: United States
• Language: English

Related Subjects

550301* -- Cytology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AGGLUTININS
ANIMAL CELLS
ANIMALS
ANTIBODIES
AZINES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CARCINOGENS
CELL CULTURES
CELL PROLIFERATION
CONCANAVALIN
CONNECTIVE TISSUE CELLS
DYNAMIC FUNCTION STUDIES
ESTERS
GUINEA PIGS
HEMAGGLUTININS
HETEROCYCLIC COMPOUNDS
HYDROGEN ISOTOPES
ISOTOPES
LABELLED COMPOUNDS
LECTINS
LIGHT NUCLEI
MACROPHAGES
MAMMALS
MITOGENS
NUCLEI
NUCLEOSIDES
NUCLEOTIDES
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHAGOCYTES
PHORBOL ESTERS
PYRIMIDINES
RADIOISOTOPES
RIBOSIDES
RODENTS
SOMATIC CELLS
THYMIDINE
THYMOCYTES
TRITIUM
VERTEBRATES
YEARS LIVING RADIOISOTOPES